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Pre-clinical models (animal or cell models recognized by ALSUntangled reviewers to be relevant to ALS)

Grade C: One or more peer-reviewed publication(s) reporting benefits in flawed studies.

Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.

Clenbuterol 

March 11, 2026

Clenbuterol’s effects on neuroinflammation, muscle hypertrophy, and mitochondrial activity appear potentially relevant to ALS disease pathology. Data in murine models of motor neurondisease as well as two small flawed clinical trials in PALS are also somewhat promising but due to the small sample sizes, lack of randomization or blind-ing or placebo controls, these must be […]

Alpha Lipoic Acid

May 28, 2025

ALA has several plausible mechanisms for slowing ALS progression, including enhancing energy production, reducing oxidative stress as a potent antioxidant and anti inflammation. Preclinical studies demonstrated better motor function and improved survival. One open label study suggested improved QOL and fatigue when administered as a palladium lipoic acid complex, but motor function was not assessed. […]

Zinc 

March 17, 2025

Zinc has plausible mechanisms for modulating ALS progression, specifically with its roles in oxidative stress reduction and stabilization of SOD1 structure and function. Preclinical data has demonstrated potential benefits in slowing ALS progression at moderate doses in mouse models, but high doses without additional supplementation of copper were shown to be harmful. Clinical data on […]

Caffeine

June 16, 2023

Caffeine is inexpensive, reasonably safe at doses of under 400 mg daily, and has plausible mechanisms by which it could slow ALS progression. However, data from pre-clinical models are contradictory and a two cohort studies showed no clear relationship between caffeine intake and ALS progression. Based on all this, we cannot endorse caffeine as anALS […]

Ketogenic Diets

October 21, 2021

Ketogenic diets have plausible mechanisms for treating ALS. One flawed preclinical study and two Patients Like Me participants reported benefits; these were not independently verified. Two other Patients Like Me participants and one patient underthe care of an ALSUntangled investigator did not show benefits. A trial of a ketogenic diet was only able to enroll […]

Vitamin C

July 14, 2021

Vitamin C is safe and inexpensive. As an antioxidant, it has a plausible mechanism for influencing the course of neurodegenerative diseases. Two flawed preclinical studies by the same group showed benefits in a mouse model of familial ALS. There are two case reports in which it was associated with improvement. However, there are multiple possible […]

Melatonin

June 2, 2021

Melatonin has plausible mechanisms, some positive (and some negative) pre-clinical data, and two case reports in which it was part of a cocktail of treatments associated with recovery of lost motor function. As we have stated previously, there aremultiple possible explanations for cases like these. There was also a very small, flawed retrospective study suggesting […]

Light Therapy

March 12, 2021

Light therapy has not yet been convincingly shown to help people with ALS. However, at specific wavelengths and energy densities, LT appears safe and has theoretically plausible mechanisms. There is a single case report suggesting benefits for light therapy in ALS, but it contains in sufficient detail to independently confirm diagnosis or treatment benefit. Further […]

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